Several new drugs for depression work much faster than traditional antidepressants, sometimes after a single dose. These agents target three different brain systems: NMDA glutamate receptors, GABA A neurosteroid and benzodiazepine sites, and serotonin 2A/2C receptors. Despite their different targets, all trigger rapid neuroplasticity—the brain's ability to reorganize—which correlates with their fast antidepressant effects. Some of these drugs, called neuroplastogens, induce neuroplasticity without altering mental state. Others, called psychoplastogens, cause dissociation or hallucinatory experiences. There is debate whether these mental changes are necessary for the antidepressant effect or are unwanted side effects. These new treatments are expected to transform the management of major depressive disorder.
Psychoactive substances like psychedelics, cannabis, and stimulants are being reconsidered for therapeutic use, but their histories in non-medical contexts raise ethical and regulatory challenges. This review examines the ethical issues shaping research and prescribing, highlighting diverse perspectives from Indigenous, philosophical, psychiatric, and user communities. Key concerns include balancing therapeutic benefits against misuse risks, ensuring rigorous science, and addressing sociopolitical factors that influence public perception and policy. The article calls for evidence-based frameworks that prioritize patient safety and recognize social and commercial determinants of health, extending ethics beyond prescribing. It critically assesses the promise and limitations of repurposing these substances for contemporary psychiatric practice.